Togaviruses are a common cause of epidemic viral encephalitis. Morbidity and mortality varies with the virus and age of the person affected but is usually associated with the acute phase of the illness. No specific treatment is currently available. Neurologic damage may be related to virus replication and/or the inflammation induced by the virus. Sindbis virus (SV), an alphavirus, causes an acute encephalitis in mice in which mortality is dependent on the age of the mouse and strain of the virus used. The inflammatory response depends on sensitized T cells, monocytes and B cells but the timing of the entrance of each of these cells is not known. Inflammatory cells peak first in the cerebrospinal fluid, then the meninges and last the brain parenchyma. Cells in each of these compartments will be identified throughout the period of virus replication and inflammation by peroxidase staining using monoclonal antibodies against lymphocyte surface markers (Thy 1, Lyt-1, Lyt-2, RA3-2C2, and IgD). Nonspecific esterase staining will be used to identify monocytes. It is postulated that tissue mast cells may be important in facilitating the movement of monocytes across the blood brain barrier. This possibility will be explored by depleting normal mice of mast cell mediators, by blocking mediator (histamine and serotonin) receptors, and by using mast cell deficient mice (WBB6F-W/WV). These mice, and appropriate controls, will be infected with a nonlethal strain of SV. Mast cells, virus growth, and inflammation will be quantitated and blood brain barrier function will be measured to determine the role of mast cells on the generation of the mononuclear inflammatory response. Mice with fatal encephalitis caused by a neuroadapted strain of SV can be protected with immune serum given after encephalitis is established. To analyze the mechanism of antibody protection, monoclonal antibodies of IgG1, IgG2A, IgG2B, IgG3, IgA and IgM subclasses will be prepared against the three structural proteins (E1, E2, and C) of SV. These antibodies will be characterized as to isotype, specificity and biological function using protection, virus neutralization, passage into the cerebrospinal fluid and brain, ability to block T cell-mediated cytotoxicity, and function in antibody dependent cellular cytotoxicity.